Enantiocontrolled Preparation of ϒ-Substituted Cyclohexenones : Synthesis and Kinase Activity Assays of Cyclopropyl-Fused Cyclohexane Nucleosides
Jurado Moreno, Sergio (Universitat Autònoma de Barcelona. Departament de Química)
Domínguez Pérez, Beatriz (Universitat Autònoma de Barcelona. Departament de Química)
Illa, Ona (Universitat Autònoma de Barcelona. Departament de Química)
Balzarini, Jan (Katholieke Universiteit Leuven. Laboratory of Virology and Chemotherapy)
Busqué Sánchez, Félix (Universitat Autònoma de Barcelona. Departament de Química)
Alibes, Ramón (Universitat Autònoma de Barcelona. Departament de Química)

Date:	2022
Abstract:	The enantioselective preparation of the two isomers of 4-hydroxy-2-cyclohexanone derivatives 1a,b was achieved, starting from a common cyclohexenone, through asymmetric transfer hydrogenation (ATH) reactions using bifunctional ruthenium catalysts. From these versatile intermediates, a stereoselective route to a cytosine analogue built on a bicyclo [4. 1. 0]heptane scaffold is described. Nucleoside kinase activity assays with this cyclopropyl-fused cyclohexane nucleoside, together with other related nucleosides (2a-e), were performed, showing that thymine- and guanine- containing compounds have affinity for herpes simplex virus Type 1 (HSV-1) thymidine kinase (TK) but not for human cytosolic TK-1, thus pointing to their selectivity for herpetic TKs but not cellular TKs.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-191 Agencia Estatal de Investigación CTQ2016-75363-R Agencia Estatal de Investigación PID2019-106403RB-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Asymmetric synthesis ; Carbocyclic nucleosides ; HSV-1 thymidine kinase ; Enzymatic assays
Published in:	International journal of molecular sciences, Vol. 23, Issue 17 (September 2022) , art. 9704, ISSN 1422-0067

DOI: 10.3390/ijms23179704
PMID: 36077100

15 p, 1.6 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > Synthesis of Bioactive Organic Compounds and Functional Materials (SynOrgFUN)
Articles > Research articles
Articles > Published articles